Context: There is growing evidence for interactions between the regulation of body fat and the immune system. Studies of knockout mice indicate that IL-1 has an anti-obesity effect.

Objective: To investigate our hypothesis that common polymorphisms of the IL-1 system, which are associated with IL-1 activity, also are associated with fat mass.

Design, Setting and Study Subjects: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18-20 yr old men (n = 1068), mostly Caucasian, from the Gothenburg area (Sweden). Three different polymorphisms, IL-1 +3953 C/T, IL-1 -31 T/C, and IL-1 receptor antagonist (IL-1RN) variable number tandem repeat (VNTR) of 86 bp, were investigated in relation to body fat mass.

Main Outcome Measure: The main outcome measures were genotype distributions and their association with body fat mass in different compartments, measured with Dual energy x-ray Absorptiometry (DXA).

Results: Carriers of the T variant (CT and TT) of the +3953 C to T (F_T=0.25) IL-1 gene polymorphism had significantly lower total fat mass (P = 0.013) and also significantly reduced arm, leg, and trunk fat compared with CC individuals. IL-1RN*2 carriers with two repeats of the IL-1RN VNTR polymorphism had increased total fat (P = 0.036), serum leptin, fat of trunk and arm, as well as serum levels of IL-1RN and IL-1RN production ex vivo. The IL-1-31 polymorphism did not correlate with the fat measurements.

Conclusions: The IL-1 system, recently shown to affect fat mass in experimental animals, contains gene polymorphisms that are associated with fat mass in young men.